Synaptic Plasticity Relies On Rate And Temporal Code In The Hippocampus

Neural coding is one of the key issues in neuroscience. Classic theory assumes that rate code, the instantaneous frequency of a burst of action potentials (APs), is used by neurons to transmit information. In contrast, temporal code, the precise timing of APs on a millisecond time scale is also believed to be used by neurons.Activity-dependent synaptic plasticity, which is mostly studied in hippocampus, is generally believed to be the cellular basis of learning and memory. Vast evidence has demonstrated that a brief high-frequency stimulation (HFS) or low-frequency stimulation (LFS) at Schaffer collaterals can induce LTP or LTD in the hippocampal CA1area respectively. Most forms of LTP and LTD are dependent on the activation of NMD A receptors for induction and the trafficking of AMPA receptors for expression. These developments are consistent with rate code hypothesis. However, spike-timing dependent pLasticity(STDP) is believed to be consistent with temporal code. Nevertheless, a more physiological protocol, theta burst stimulation (TBS),which is short bursts of stimuli at theta frequency to induce LTP is also consistent with temporal code because either LTP or LTD can be induced by TBS at the peak or trough of the hippocampal field theta waves, demonstrating the rule of the timing between TBS-produced bursts and endogenous field oscillations. TBS is always thought to mimic the short burst firing pattern of the CA1pyramidal neurons. Since Schaffer collaterals can activate both pyramidal and GABAergic neurons of the CA1area and GABAergic neurons often show longer burst. However, the effect of GABAergic firing pattern to synaptic plasticity is still unknown until now.Therefore, activity patterns mimicking the CA1GABAergic neurons were used to stimulate Schaffer collaterals and the field excitatory postsynaptic potentials (fEPSPs) were recorded in hippocampal CA1area of freely moving rat and slices. Here, we discovered a particular pattern, long burst high-frequency stimulations (LHS,15pulses at100Hz,60trains at5Hz) but not other similar protocols was able to induce a novel LTD reliably. The LTD was still induced with the present of the NMD A receptor antagonists AP5or MK801, or the mGlu receptor antagonist MCPG, which as expected are able to block LFS-induced LTD. However, the LTD was completely blocked by antagonists to either of the GABAa or mACh receptors. However, it can be blocked by Tat-GluR23Y peptide, indicating it still needed endocytosis of AMPA receptors, the known mechanisms underlying LTD expression.These findings demonstrate that long burst high frequency stimulation mimicking an activity of the CA1GABAergic neurons, induces a novel form of LTD-LTDLHS-LTDLHS depends on GABAA and mACh receptors and its expression relies on endocytosis of AMPA receptors.Our findings is an important supplement of existing form and mechanisms of the classic synaptic plasticity in hippocampus. Furthermore, it suggests a possibility that rate and temporal code could work together through a particular pattern of high-freuqency burst activity in the local circuit of the hippocampal CA1neurons.